The overarching goal of this research program is to elucidate the evolutionary trajectories of cancer metastases, allowing us to identify when key genomic and epigenomic changes occur in tumor evolution, and what their role is in driving metastasis.

We will achieve this objective through three main aims:

1. Leverage existing whole-genome sequences of ~4,000 cancer metastases to obtain the typical evolutionary trajectories of cancer metastases across cancer types. To do this, I will employ “molecular archeology of cancer” approaches that I have pioneered to infer cancer’s evolutionary history and subclonal architecture from sequencing data.
2. Collect and sequence matched primary/metastasis pairs...

Read More

The overarching goal of this research program is to elucidate the evolutionary trajectories of cancer metastases, allowing us to identify when key genomic and epigenomic changes occur in tumor evolution, and what their role is in driving metastasis.

We will achieve this objective through three main aims:

1. Leverage existing whole-genome sequences of ~4,000 cancer metastases to obtain the typical evolutionary trajectories of cancer metastases across cancer types. To do this, I will employ “molecular archeology of cancer” approaches that I have pioneered to infer cancer’s evolutionary history and subclonal architecture from sequencing data.
2. Collect and sequence matched primary/metastasis pairs from the institute tissue bank and through a dedicated autopsy program and apply existing and newly developed molecular archeology of cancer approaches to construct detailed timelines of tumor evolution from early tumor development through to metastasis. We will focus on pancreatic cancer, due to the clear clinical need, and on colorectal cancer with liver metastases, for which the institute tissue bank holds hundreds of samples.
3. Develop novel molecular archeology of cancer approaches leveraging the tumor methylome to time events in tumor evolution, and through whole-genome bisulfite sequencing of primary/metastasis pairs from aim 2, construct detailed integrated evolutionary trajectories, including both genomic and epigenomic events.

This project will lead to key biological insights of the evolutionary history of cancer metastases, which cause 90% of cancer-related deaths. In addition, this work will have profound clinical implications, e.g., in stratifying patients for closer follow-up or more aggressive treatment, and in the development of early detection strategies aiming to detect and cure cancers before they metastasize.

Read Less